The Medical University of South Carolina will establish a Multidisciplinary Clinical Research Center (MCRC) for the Study of Rheumatic Diseases in African-Americans. This MCRC will focus on scleroderma (SSc) and systemic lupus erythematosus (SLE), two rheumatic diseases that disproportionately affect the African-American community. Outstanding leadership in three key areas - Rheumatology, Biometry/Epidemiology, and Health Services Research - provides a framework for successful design and implementation of meaningful clinical research in this understudied population of patients. Three projects and three supporting cores are proposed. Project A is designed to study the interactions between TGF-beta and sphingolipid signaling pathways in SSc and normal fibroblasts. The proposed studies will elucidate this heretofore-unknown interaction to shed light on the mechanism whereby TGF-beta signaling is integrated with other cellular signaling pathways leading to fibrosis. Project B addresses an important understudied area, namely psychosocial aspects of female adolescents with SLE, the majority of whom are African-American. MCRC investigators will assess the associations between adaptational processes and adjustment and health-related quality of life, and will conduct an interventional trial designed to enhance adjustment and quality of life for these patients. Project C will address the important issue of divergent racial trends in morbidity from lupus nephritis. Mortality has increased for African-American lupus patients while remaining stable in Caucasian lupus patients, and this divergence cannot be accounted for by differences in socioeconomic status alone. Utilizing the unique resources of the Carolina Lupus Study and the sea island Gullah population, MCRC investigators will address genetic and environmental influences on the development and progression of lupus nephritis. Each of these projects, as well as future pilot projects to be developed by the MCRC, will be served by two Cores: (1) a Methodology Core will provide rigorous methodological and biostatistical support; and (2) a Patient Resource Core will assure MCRC investigators access to a population of African-American patients who are clinically well characterized and from whom biological samples are obtained and stored. This MCRC will facilitate the translation of basic research into the clinical arena, support much needed behavioral research, and conduct epidemiology and health services research on rheumatic diseases affecting minorities and women disproportionately, thus exemplifying the "cross-cutting" nature of research proposed in NIAMS's strategic plan.